PPARα attenuates the proinflammatory response in activated mesangial cells

Kono K, Kamijo Y, Hora K, Takahashi K, Higuchi M, Kiyosawa K, Shigematsu H, Gonzalez FJ, Aoyama T. PPAR alpha attenuates the proinflammatory response in activated mesangial cells. Am J Physiol Renal Physiol 296: F328-F336, 2009. First published November 26, 2008; doi:10.1152/ajprenal.00484.2007.-The activated mesangial cell is an important therapeutic target for the control of glomerulonephritis. The peroxisome proliferator-activated receptor alpha (PPAR alpha) has attracted considerable attention for its anti-inflammatory effects; however, its roles in the mesangial cells remain unknown. To determine the anti-inflammatory function of PPAR alpha in mesangial cells, wild-type and Ppara-null cultured mesangial cells were exposed to lipopolysaccharide (LPS). LPS treatment caused enhanced proinflammatory responses in the Ppara-null cells compared with wildtype cells, as revealed by the induction of interleukin-6, enhanced cell proliferation, and the activation of the nuclear factor (NF)-kappa B signaling pathway. In wild-type cells resistant to inflammation, constitutive expression of PPAR alpha was undetectable. However, LPS treatment induced the significant appearance and substantial activation of PPAR alpha, which would attenuate the proinflammatory responses through its antagonizing effects on the NF-kappa B signaling pathway. The induction of PPAR alpha was coincident with the appearance of alpha-smooth muscle actin, which might be associated with the phenotypic changes of mesangial cells. Moreover, another examination using LPS-injected wild-type mice demonstrated the appearance of PPAR alpha-positive cells in glomeruli, suggesting in vivo correlation with PPAR alpha induction. These results suggest that PPAR alpha plays crucial roles in the attenuation of inflammatory response in activated mesangial cells. PPAR alpha might be a novel therapeutic target against glomerular diseases.